Reaction of N-substituted exo-2-hydroxy-5-oxo-4-oxatricyclo[4.2.1.0 3,7]nonane-endo-9-carboxamides with acetic acid

Article abstract of DOI:10.1134/S1070428010060096

Acylation of N-substituted exo-2-hydroxy-5-oxo-4-oxatricyclo[4.2.1.0 ^3,7]nonane-endo-9-carboxamides on heating in boiling glacial acetic acid gave the corresponding trans-diacetoxy imides of the norbornane series. The effect of the reaction tim

Full text of DOI:10.1134/S1070428010060096

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 6, pp. 823–829. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © V.A. Pal’chikov, I.N. Tarabara, I.V. Omel’chenko, O.V. Shishkin, L.I. Kas'yan, 2010, published in Zhurnal Organicheskoi Khimii,
2010, Vol. 46, No. 6, pp. 831–836.
Reaction of N-Substituted exo-2-Hydroxy-5-oxo-
4-oxatricyclo[4.2.1.03,7]nonane-endo-9-carboxamides
with Acetic Acid
V. A. Pal’chikova, I. N. Tarabaraa, I. V. Omel’chenkob, O. V. Shishkinb, and L. I. Kas’yana
a Oles’Gonchar Dnepropetrovsk National University, pr. Gagarina 72, Dnepropetrovsk, 49625 Ukraine
e-mail: palchikoff@mail.ru
b Institute of Single Crystals, National Academy of Sciences of Ukraine, Kharkov, Ukraine
Received October 27, 2009
Abstract—Acylation of N-substituted exo-2-hydroxy-5-oxo-4-oxatricyclo[4.2.1.03,7]nonane-endo-9-carbox-
amides on heating in boiling glacial acetic acid gave the corresponding trans-diacetoxy imides of the nor-
bornane series. The effect of the reaction time on the product composition was studied in the reaction with
exo-2-hydroxy-N-(4-methylphenyl)-5-oxo-4-oxatricyclo[4.2.1.03,7]nonane-endo-9-carboxamide. The structure
1
of the resulting norbornane-2,3-dicarboximides was confirmed by IR, H NMR, and mass spectra, and the
structure of N-(2,5-dimethylphenyl)-exo-2,endo-3-diacetoxybicyclo[2.2.1]heptan-endo-5,endo-6-dicarbox-
imide was additionally proved by X-ray analysis.
DOI: 10.1134/S1070428010060096
Imides of the norbornane (bicyclo[2.2.1]heptane)
series were studied to a considerably lesser extent then
their unsaturated analogs. However, these compounds
were shown to exhibit anxiolytic and/or antidepressant
activity [1]; some imides, e.g., Tandospirone (Ia),
showed affinity for 5-HT1A and 5-HT2A serotonin
receptors [2]. Some imides may be used for the treat-
ment of blood circulation system [3], compounds Ib
Scheme 1.
O
O
O
N
R2
N
R
N
N
R1
O
N
R
N
N
R3
( )n
O
O
N
O
O
O
Ia
Ib
Ic
O
O
5% H2SO4
60°C, 4 h
R
R
MeCO3H
O
HO
N
N
N
O
O
O
OH
Id
Ie
O
R
AcO
Ac2O, H2SO4, 6 h
N
O
OAc
If
R = H, 2-MeO, 3-MeO, 4-MeO, 2-Cl, 3-Cl, 4-Cl, 4-Br, 2-HOCO, 3-HOCO, 4-HOCO.
823

PAL’CHIKOV et al.
824
(R1 = aryl, hetaryl; R2, R3 = alkyl, cycloalkyl; n = 2–4)
are antiarrhythmic [4] and sedative agents [5]; they also
act as stabilizers against UV irradiation [6]. Stereo-
chemistry of the oxidation of N-aryl imides Ic and Id
derived from endo- and exo-bicyclo[2.2.1]hept-5-ene-
2,3-dicarboxylic acids was examined; it was found
that, regardless of the nature and orientation of substit-
uents, the reaction of these compounds with peroxy-
acetic acid generated in situ gave the corresponding
epoxy derivatives. The exo-oriented oxirane ring was
readily opened by the action of 5% aqueous sulfuric
acid on heating to produce trans-dihydroxy imides Ie.
The latter were converted into acetates If by treatment
with acetic anhydride [7] (Scheme 1).
boiling glacial acetic acid over a period of 32–48 h we
obtained compounds IIIa–IIIf (Scheme 2). Imides
IIId and IIIe were described previously [7]; however,
their IR and 1H NMR spectra were not given.
Using N-(4-tolyl) derivative IIa as an example we
examined how the reaction time affects the composi-
tion of products. The product mixtures were analyzed
1
by thin-layer chromatography and H NMR spectros-
copy. Scheme 3 illustrates a probable transformation
sequence in a simplified form. The compositions of the
reaction mixtures, depending on the reaction time, are
given in table. These data are consistent with the as-
sumed reaction scheme. In the first step, acylation of
the hydroxy group in lactone IIa occurs, next follows
acid-catalyzed isomerization of acetoxy lactone IV
into acetoxy imide V, and acylation of the endo-
oriented hydroxy group leads to the final product,
trans-diacetoxy imide IIIa whose fraction sharply
increases after heating for 8 h.
Scheme 2.
AcOH, reflux
32–48 h
HO
AcO
O
CONHR
R
N
O
OAc
Individual compounds IIIa and IV were isolated by
column chromatography on silica gel from the reaction
mixture obtained in run no. 4. We also isolated a frac-
tion (21%) containing amido lactone IV and inter-
mediate V. The latter was not detected in the reaction
mixture by NMR spectroscopy; presumably, it was
formed as a result of unexpected isomerization of com-
pound IV during chromatography. By special experi-
ments we showed that pure acetoxy lactone IV is con-
verted into final product IIIa in 91% yield on heating
in boiling acetic acid over a period of 26 h. Diacetates
IIIa, VI, and VII were also synthesized by independ-
ent method, by reaction of trans-dihydroxy imides
VIIIa–VIIIc [8] with acetic acid (Scheme 4).
O
O
IIa–IIf
IIIa–IIIf
R = 4-MeC6H4 (a), 2,6-Me2C6H3 (b), 2,5-Me2C6H3 (c),
4-BrC6H4 (d), 4-MeOC6H4 (e), cyclo-C6H11 (f).
The present work was aimed at developing a new
procedure for the synthesis of potentially biologically
active N-aryl-exo-2,endo-3-diacetoxybicyclo[2.2.1]-
heptane-endo-5,endo-6-dicarboximides by acylation of
the corresponding N-aryl-exo-2-hydroxy-5-oxo-4-oxa-
tricyclo[4.2.1.03,7]nonane-endo-9-carboxamides IIa–
IIf and studying the effect of the reaction time on the
product composition. Initial N-aryl-exo-2-hydroxy-5-
oxo-4-oxatricyclo[4.2.1.03,7]nonane-endo-9-carbox-
amides IIa–IIf were prepared according to the proce-
dures reported in [8]. By heating amides IIa–IIf in
The structure of trans-diacetoxy imide IIIa was
additionally confirmed by its transformation into
Scheme 3.
Me
Me
8
H+
1
HO
AcO
AcO
AcOH
2
Me
9
O
7
3
6
N
N
O
H
O
O
H
N
O
O
OH
5
4
O
O
IIa
IV
V
7
1
AcO
2
6
Me
O
AcOH
3
4
5
N
OAc
O
IIIa
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

REACTION OF N-SUBSTITUTED exo-2-HYDROXY-5-OXO-4-OXATRICYCLO...
825
Scheme 4.
Reaction of amido lactone IIa with acetic acid
Composition of products,a %
HO
AcO
AcOH, reflux
40–48 h
Run
no.
Reaction
time, h
O
O
IV
V
IIIa
R
R
b46b
00
49
33
00
00
00
000
000
000
063
087
100
N
N
OH
VIIIa–VIIIc
OAc
1
2
3
4
5
6
04
06
08
16
24
32
O
O
51
IIIa, VI, VII
67
VI, VIIIa, R = H; VII, VIIIb, R = Me;
IIIa, VIIIc, R = 4-MeC6H4.
37
13
00
known acid IX [9] on heating in 10% aqueous sodium
carbonate, followed by treatment with hydrochloric
acid. Acylation of the exo-oriented hydroxy group in
carboxylic acid IX was accomplished by heating in
boiling glacial acetic acid. Compound X thus obtained
(Scheme 5) was reported previously [10], but neither
its properties nor spectral parameters were given.
According to the 1H NMR data.
The reaction mixture also contained 54% of initial amido
a
b
lactone IIa.
1.429(5) Å, which is typical of unconjugated bonds
(average bond length 1.426 Å [15]), and the aryl group
is turned through an angle of 81.3(5)° [torsion angle
C8N1C14C15] with respect to the heteroring, indicating
the absence of conjugation between the imide fragment
and the aromatic ring. Molecules IIIc in crystal are
characterized by disordering of the aryl fragment by
two positions with equal populations due to rotation
about the N1–C14 bond.
The molecular and crystalline structures of com-
pound IIIc were determined by X-ray analysis (see
figure). The five-membered C1C2C3C7C6 and
C3C4C5C6C7 rings in molecule IIIc have an envelope
conformation with the C7 atom deviating by 0.877 and
0.896 Å, respectively, from the planes formed by the
other atoms in the above rings. The six-membered
C1C2C3C4C5C6 ring adopts a boat conformation with
the following puckering parameters [11]: S = 1.13, θ =
87.4°, ψ = 1.6°. Such configuration of the cage-like
fragment in imide IIIc is typical of analogous com-
pounds [12, 13].
The substituent on C1 occupies exo position, and
the substituent on C2 is oriented endo; the torsion
angles C3C2C1O5 and C6C1C2O3 are 120.5(3) and
128.0(3)°, respectively. The endo orientation of the
acetoxy group on C2 is responsible for shortened intra-
molecular contact O3···C8 2.71 Å (the sum of the cor-
responding van der Waals radii is 3.00 Å [14]). The
heterocyclic fragment is oriented endo relative to the
bicyclic skeleton [the torsion angle C6C4C5C9 is
–124.1(2)°]. The imide nitrogen atom has a planar–
trigonal bond configuration [the sum of the bond
angles at the nitrogen atom is 360(1)°], as in analogous
structures [12, 13]. The N1–C14 bond length is
The structure of the other compounds was con-
1
firmed by their IR and H NMR spectra. In the IR
spectra of IIIa–IIIf, VI, and VII, the imide fragment
gave rise to absorption bands at 1777–1735 and 1735–
1705 cm–1 belonging to symmetric and antisymmetric
stretching vibrations of the carbonyl groups; the low-
frequency band had considerably higher intensity [16].
1
The H NMR spectra of lactones IV and X were
characterized by similar positions of signals from
protons in the bicyclic skeleton. The amide NH
proton signal in the spectrum of IV was located at
δ 10.07 ppm, and compound X displayed a singlet
from the carboxy proton at δ (12.85 ppm.
1
The H NMR spectra of IIIa–IIIf, VI, and VII
contained some characteristic signals: a doublet from
1-H at δ 2.62–2.75 ppm (3J1,6 = 5.3–6.0 Hz), a singlet
from endo-2-H at δ 4.36–4.88 ppm, and a signal from
exo-3-H at δ 4.77–4.91 ppm. The latter signal appears
Scheme 5.
AcO
HO
AcO
(1) 10% Na2CO3, reflux, 5 min
(2) 20% HCl
Me
O
AcOH, reflux, 48h
93%
COOH
COOH
88%
N
O
O
OAc
O
O
O
IIIa
IX
X
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

PAL’CHIKOV et al.
X-Ray diffraction data for compound IIIc.
826
C7
C1
C5
C6
O5
Monoclinic crystals, C21H21NO6, with the following
unit cell parameters (at 20°C): a = 26.962(4), b =
7.8475(7), c = 23.744(6) Å; β = 124.52(2)°; V =
O2
N1
C13
C9
C3 C4
C20A
C15
C12
C2
O4
4139(1) Å3; M 383.39; Z = 8; space group C2/c; dcalc
=
C8
O1
C14
1.230 g/cm3; μ(MoKα) = 0.091 mm–1; F(000) = 1616.
O6
O3
C10
The unit cell parameters and intensities of 14825 re-
C21B
C16
C17
C19
C20B
C11
flections (6883 of which were independent with Rint
=
0.092) were measured on an Xcalibur-3 diffractometer
(MoKα irradiation, CCD detector, graphite monochro-
mator, ω scanning, 2θmax = 50°). The structure was
solved by the direct method using SHELXTL software
package [18]. The C15–C20A, C16–C21B, C19–C20B, and
C18–C21A bond lengths in the disordered fragment were
restricted to 1.506(5) Å in the refinement procedure.
The positions of hydrogen atoms were determined on
the basis of geometry considerations and were refined
according to the riding model with Uiso = nUeq (n = 1.5
for methyl groups; n = 1.2 for other hydrogen atoms).
The structure was refined by F2 using full-matrix least-
squares procedure in anisotropic approximation for
non-hydrogen atoms to wR2 = 0.189 (for 3282 reflec-
tions) and R1 = 0.066 [for 1268 reflections with F >
4σ(F)], S = 0.84. The complete set of crystallographic
data, including coordinates of atoms, was deposited to
the Cambridge Crystallographic Data Center (entry
no. CCDC 721245).
C18
C21A
Structure of the molecule of N-(2,5-dimethylphenyl)-exo-
2,endo-3-diacetoxybicyclo[2.2.1]heptane-endo-5,endo-6-di-
carboximide (IIIc) according to the X-ray diffraction data.
in the spectrum of VII as a doublet as a result of cou-
pling with 4-H with a coupling constant J of 5.1 Hz. In
the H NMR spectra of the other compounds, the exo-
1
3-H proton resonates as a broadened singlet. Signals
from nonequivalent exo-protons on C5 and C6 were
located in the region δ 3.12–3.73 ppm, and the differ-
ence between their chemical shifts was ∆δ = 0.16–
0.36 ppm. Methyl protons in the exo- and endo-
oriented acetoxy groups resonated at δ 2.00–2.03 and
1.68–1.88 ppm, respectively, which is very consistent
with published data for structurally related compounds
1
trans-Diacetoxy imides IIIa–IIIf, VI, and VII
(general procedure). A solution of 2 mmol of amido
lactone IIa–IIf or trans-dihydroxy imide VIIIa–VIIIc
in 15 ml of glacial acetic acid was heated under reflux
until the reaction was complete (TLC, 32–48 h). The
solvent was distilled off under reduced pressure, and
the residue was purified by recrystallization from
propan-2-ol.
[17]. The H NMR spectrum of monoacetoxy imide V
showed a different mutual arrangement of the 2-H and
3-H signals (δ 4.38 and 4.33 ppm, respectively) than in
the spectra of diacetoxy derivatives IIIa–IIIf, VI, VII.
In addition, the spectrum of V contained a doublet
from the hydroxy proton at δ 5.56 ppm (3J = 3.9 Hz).
The spectra of compounds IIIa–IIIf and V–VII also
contained complete sets of signals from the N-aryl
imide fragment.
exo-2,endo-3-Diacetoxy-N-(4-methylphenyl)bi-
cyclo[2.2.1]heptane-endo-5,endo-6-dicarboximide
(IIIa). Yield 0.65 g (88%), mp 191–193°C, Rf 0.33
(diethyl ether). IR spectrum, ν, cm–1: 2990, 1735,
EXPERIMENTAL
1
The IR spectra were recorded in KBr on UR-20 and
1710, 1520, 1390, 1240, 1195, 1060, 1040. H NMR
1
Paragon 500 FT-IR spectrometers. The H NMR spec-
spectrum, δ, ppm: 1.69 s (3H, endo-AcO), 1.77 d (1H,
anti-7-H, J = 11.3 Hz), 1.97 d (1H, syn-7-H), 2.03 s
2
tra were measured on a Varian VXR spectrometer at
300 MHz from solutions in DMSO-d6 using tetra-
methylsilane as internal reference. The mass spectrum
(electron impact, 70 eV) was obtained on a Varian
1200L instrument. The progress of reactions and the
purity of products were monitored by TLC on Silufol
UV-254 plates using diethyl ether (A) or propan-2-ol
(B) as eluent; development with iodine vapor. The
elemental compositions were determined on a Carlo
Erba analyzer.
(3H, exo-AcO), 2.35 s (3H, CH3), 2.73 d (1H, 1-H,
3J1,6 = 5.7 Hz), 3.05 m (1H, 4-H), 3.33 d.d (1H, 5-H,
3
3J4,5 = 5.1, J5,6 = 9.9 Hz), 3.55 d.d (1H, 6-H), 4.65 s
(1H, 2-H), 4.88 br.s (1H, 3-H), 7.12 d (2H, Harom),
7.33 d (2H, Harom). Mass spectrum, m/z (Irel, %): 371
(44.5) [M]+, 372 (8.5) [M + 1]+, 329 (6.9), 286 (18.2),
269 (14.9), 241 (21.6), 206 (17.7), 108 (29.2), 107
(100), 79 (45.8). Found, %: C 64.77; H 5.61; N 3.89.
C20H21NO6. Calculated, %: C 64.68; H 5.70; N 3.77.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

REACTION OF N-SUBSTITUTED exo-2-HYDROXY-5-OXO-4-OXATRICYCLO...
827
9.8 Hz), 3.54 d.d (1H, 6-H), 3.79 s (3H, OCH3), 4.64 s
(1H, 2-H), 4.87 br.s (1H, 3-H), 7.07 d (2H, Harom),
7.16 d (2H, Harom).
exo-2,endo-3-Diacetoxy-N-(2,6-dimethylphenyl)-
bicyclo[2.2.1]heptane-endo-5,endo-6-dicarboximide
(IIIb). Yield 0.60 g (78%), mp 210–212°C, Rf 0.62
(diethyl ether). IR spectrum, ν, cm–1: 3005, 1740,
exo-2,endo-3-Diacetoxy-N-cyclohexylbicyclo-
[2.2.1]heptane-endo-5,endo-6-dicarboximide (IIIf).
Yield 0.66 g (91%), mp 98–100°C, Rf 0.79 (diethyl
ether). IR spectrum, ν, cm–1: 2950, 1745, 1705, 1380,
1
1710, 1485, 1370, 1245, 1230, 1190, 1050. H NMR
spectrum, δ, ppm: 1.73 s (3H, endo-AcO), 1.77 d (1H,
2
anti-7-H, J = 11.4 Hz), 2.00 s (3H, exo-AcO), 2.02 d
1
(1H, syn-7-H), 2.04 s (3H, CH3), 2.28 s (3H, CH3),
1245, 1200, 1060. H NMR spectrum, δ, ppm: 1.11–
3
2.75 d (1H, 1-H, J1,6 = 5.4 Hz), 3.11 m (1H, 4-H),
1.31 (3H, C6H11), 1.54–1.68 (5H, C6H11), 1.78 d (1H,
anti-7-H), 1.88 s (3H, endo-AcO), 1.90 d (1H, syn-
7-H), 2.00 s (3H, exo-AcO), 2.00–2.10 (2H, C6H11),
3
3
3.52 d.d (1H, 5-H, J4,5 = 4.7, J5,6 = 10.3 Hz), 3.73 d.d
3
(1H, 6-H), 4.88 s (1H, 2-H), 4.89 d (1H, 3-H, J3,4
=
3
5.1 Hz), 7.16–7.28 (3H, Harom). Found, %: C 65.31;
H 6.13; N 3.72. C21H23NO6. Calculated, %: C 65.44;
H 6.02; N 3.63.
2.62 d (1H, 1-H, J1,6 = 5.9 Hz), 2.98 m (1H, 4-H),
3
3
3.12 d.d (1H, 5-H, J4,5 = 5.1, J5,6 = 9.6 Hz), 3.30 d.d
(1H, 6-H), 3.83 t.t (1H, NCH), 4.45 s (1H, 2-H),
4.78 br.s (1H, 3-H). Found, %: C 62.72; H 6.81;
N 3.96. C19H25NO6. Calculated, %: C 62.80; H 6.93;
N 3.85.
exo-2,endo-3-Diacetoxy-N-(2,5-dimethylphenyl)-
bicyclo[2.2.1]heptane-endo-5,endo-6-dicarboximide
(IIIс). Yield 0.64 g (83%), mp 170–172°C, Rf 0.64
(diethyl ether). IR spectrum, ν, cm–1: 2968, 2924,
1777, 1744, 1709, 1509, 1420, 1368, 1238, 1186,
exo-2,endo-3-Diacetoxybicyclo[2.2.1]heptane-
endo-5,endo-6-dicarboximide (VI). Yield 0.51 g
(90%), oily substance, Rf 0.18 (diethyl ether). IR spec-
trum, ν, cm–1: 3291, 2933, 1744, 1700, 1372, 1238,
1
1065, 1038, 1017. H NMR spectrum, δ, ppm: 1.76 s
(3H, endo-AcO), 1.97 d (1H, anti-7-H, 2J = 10.4 Hz),
1
2.01 s (3H, exo-AcO), 2.02 s (3H, CH3), 2.23 d (1H,
1050. H NMR spectrum, δ, ppm: 1.71 d (1H, anti-
3
2
syn-7-H), 2.28 s (3H, CH3), 2.73 d (1H, 1-H, J1,6
=
=
7-H, J = 10.5 Hz), 1.88 s (3H, endo-AcO), 1.90 d
3
6.0 Hz), 3.06 m (1H, 4-H), 3.50 d.d (1H, 5-H, J4,5
(1H, syn-7-H), 2.00 s (3H, exo-AcO), 2.62 d (1H, 1-H,
3
3J1,6 = 5.3 Hz), 2.97 m (1H, 4-H), 3.12 d.d (1H, 5-H,
5.7, J5,6 = 9.9 Hz), 3.66 d.d (1H, 6-H), 4.66 s (1H,
2-H), 4.91 br.s (1H, 3-H), 6.90–6.96 (1H, Harom), 7.10–
7.26 (2H, Harom). Found, %: C 65.51; H 6.10; N 3.59.
C21H23NO6. Calculated, %: C 65.44; H 6.02; N 3.63.
3
3J4,5 = 5.0, J5,6 = 9.7 Hz), 3.30 d.d (1H, 6-H), 4.45 s
(1H, 2-H), 4.77 br.s (1H, 3-H), 7.70 s (1H, NH).
Found, %: C 55.42; H 5.49; N 5.01. C13H15NO6. Cal-
culated, %: C 55.51; H 5.38; N 4.98.
exo-2,endo-3-Diacetoxy-N-(4-bromophenyl)bi-
cyclo[2.2.1]heptane-endo-5,endo-6-dicarboximide
(IIId). Yield 0.61 g (70%), mp 208–210°C; published
data [7]: mp 133–134°C; Rf 0.66 (propan-2-ol). IR
spectrum, ν, cm–1: 2956, 1740, 1714, 1492, 1375,
exo-2,endo-3-Diacetoxy-N-methylbicyclo[2.2.1]-
heptane-endo-5,endo-6-dicarboximide (VII). Yield
0.58 g (98%), mp 149–151°C, Rf 0.24 (diethyl ether).
IR spectrum, ν, cm–1: 2980, 1770, 1735, 1710, 1435,
1
1
1239, 1044. H NMR spectrum, δ, ppm: 1.68 s (3H,
1380, 1280, 1245, 1045. H NMR spectrum, δ, ppm:
endo-AcO), 1.79 d (1H, anti-7-H, 2J = 11.4 Hz), 1.97 d
(1H, syn-7-H), 2.03 s (3H, exo-AcO), 2.74 d (1H, 1-H,
3J1, 6 = 6.0 Hz), 3.06 m (1H, 4-H), 3.35 d.d (1H,
2
1.71 d (1H, anti-7-H, J = 10.5 Hz), 1.88 s (3H, endo-
AcO), 1.92 d (1H, syn-7-H), 2.00 s (3H, exo-AcO),
3
2.63 d (1H, 1-H, J1,6 = 6.0 Hz), 2.85 s (3H, NCH3),
3
3
3
5-H, J5,6 = 10.1 Hz), 3.57 d.d (1H, 6-H), 4.63 s (1H,
2.97 m (1H, 4-H), 3.16 d.d (1H, 5-H, J4,5 = 5.0, J5,6
=
2-H), 4.90 br.s (1H, 3-H), 7.22 d (2H, Harom), 7.76 d
(2H, Harom).
9.7 Hz), 3.42 d.d (1H, 6-H), 4.36 s (1H, 2-H), 4.77 d
(1H, 3-H, J3,4 = 5.1 Hz). Found, %: C 57.01; H 5.71;
3
N 4.61. C14H17NO6. Calculated, %: C 56.94; H 5.80;
N 4.74.
exo-2,endo-3-Diacetoxy-N-(4-methoxyphenyl)bi-
cyclo[2.2.1]heptane-endo-5,endo-6-dicarboximide
(IIIe). Yield 0.59 g (76%), mp 123–125°C; published
data [7]: mp 132–134°C; Rf = 0.27 (diethyl ether). IR
spectrum, ν, cm–1: 2990, 1740, 1710, 1610, 1520,
exo-2-Acetoxy-N-(4-methylphenyl)-5-oxo-4-oxa-
tricyclo[4.2.1.03,7]nonane-endo-9-carboximide (IV).
A solution of 1.15 g (4 mmol) of amido lactone IIa in
15 ml of glacial acetic acid was heated for 16 h under
reflux. The solvent was removed under reduced pres-
sure, and the residue was passed through a column
charged with silica gel (substrate-to-sorbent ratio
1:150; eluent diethyl ether). The first fraction con-
1
1450, 1380, 1310, 1250, 1195, 1060, 1040. H NMR
spectrum, δ, ppm: 1.71 s (3H, endo-AcO), 1.77 d (1H,
2
anti-7-H, J = 11.0 Hz), 1.97 d (1H, syn-7-H), 2.03 s
3
(3H, exo-AcO), 2.73 d (1H, 1-H, J1,6 = 5.8 Hz),
3
3
3.05 m (1H, 4-H), 3.31 d.d (1H, 5-H, J4,5 = 5.0, J5,6
=
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

PAL’CHIKOV et al.
828
3
3
tained compound IIIa, yield 0.98 g (70%), Rf 0.33
(diethyl ether). The second fraction was a mixture of
compound IV and exo-2-acetoxy-endo-3-hydroxy-N-
(4-methylphenyl)bi-cyclo[2.2.1]heptane-endo-5,endo-
6-dicarboximide (V) (48 and 52%, respectively, ac-
2.77 d.d (1H, 6-H, J6,7 = 4.7, J6,9 = 11.0 Hz), 3.13 d.d
3
(1H, 9-H, J1,9 = 3.5 Hz), 3.29 m (1H, 7-H), 4.57 d
(1H, 3-H, J3,7 = 5.1 Hz), 5.09 s (1H, 2-H), 12.85 br.s
3
(1H, COOH).
This study was performed under financial support
by the State Foundation for Basic Research of Ukraine
(project no. F25.3/067).
1
cording to the H NMR data), yield 0.29 g (21%),
Rf 0.10 (diethyl ether). The third fraction contained
compound IV, yield 0.13 g (9%), mp 214–216°C,
Rf 0.10 (diethyl ether). IR spectrum, ν, cm–1: 2950,
REFERENCES
1
1765, 1675, 1030. H NMR spectrum, δ, ppm: 1.62 d
2
(1H, anti-8-H, J = 11.3 Hz), 1.93 d (1H, syn-8-H),
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Zh., Khim., 1992, no. 9O245P.
2.02 s (3H, exo-AcO), 2.25 s (3H, CH3), 2.64 br.s (1H,
3
3
2. Chilmonczyk, Z., Cybulski, M., Iskra-Jopa, J.,
Chojnacka-Wojcik, E., Tatarczynska, E., Kłodzinska, A.,
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1-H), 2.78 d.d (1H, 6-H, J6,7 = 4.5, J6,9 = 10.2 Hz),
3
3.13 d.d (1H, 9-H, J1,9 = 3.5 Hz), 3.32 m (1H, 7-H),
4.58 d (1H, 3-H, J3,7 = 4.8), 5.38 s (1H, 2-H), 7.10 d
3
(2H, Harom), 7.41 d (2H, Harom), 10.07 br.s (1H, NH).
Found, %: C 65.71; H 5.75; N 4.33. C18H19NO5. Cal-
culated, %: C 65.64; H 5.81; N 4.25.
3. Ichiro, M. and Sadao, O., US Patent no. 3850922, 1974;
Ref. Zh., Khim., 1975, no. 22O43P.
Independent synthesis of compound (IIIa).
A solution of 0.66 g (2 mmol) of compound IV in
15 ml of glacial acetic acid was heated for 26 h under
reflux. The solvent was removed under reduced pres-
sure, and the product was purified by recrystallization
from propan-2-ol. Yield 0.68 g (91%).
exo-2-Hydroxy-5-oxo-4-oxatricyclo[4.2.1.03,7]-
nonane-endo-9-carboxylic acid (IX). A suspension of
0.74 g (2 mmol) of compound IIIa in 10 ml of 10%
aqueous sodium carbonate was heated for 5 min at the
boiling point until a transparent solution was formed.
The mixture was acidified by adding dropwise 20%
hydrochloric acid until a weakly acidic reaction ac-
cording to litmus. Volatile substances were removed
under reduced pressure, the residue was treated with
12 ml of boiling acetone, the mixture was filtered
while hot, the filtrate was cooled, and the precipitate
was filtered off, washed on a filter with a small amount
of acetone, and dried in air. Yield 0.35 g (88%),
mp 200–202°C; published data [9]: mp 202–203°C.
4. Ichiro, M. and Sadao, O., US Patent no. 3850921, 1974;
Ref. Zh., Khim., 1975, no. 18O19P; Buchanan, R.L. and
Jelenevsky, A.M., US Patent no. 3980668, 1976; Ref.
Zh., Khim., 1977, no. 12O139P; Buyniski, J.P., Jelenev-
sky, A.M., and Buchanan, R.L., US Patent no. 4018767,
1977; Ref. Zh., Khim., 1978, no. 1O135P; Bucha-
nan, R.L., Woolever, J.T., and Jelenevsky, A.M., US
Patent no. 4122273, 1978; Ref. Zh., Khim., 1979,
no. 11O157P; Ichiro, M. and Sadao, O., US Patent
no. 3936449, 1976; Ref. Zh., Khim., 1976, no. 21O107P.
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exo-2-Acetoxy-5-oxo-4-oxatricyclo[4.2.1.03,7]-
nonane-endo-9-carboxylic acid (X). A solution of
0.40 g (2 mmol) of compound IX in 15 ml of glacial
acetic acid was heated under reflux until the reaction
was complete (TLC, 48 h). The solvent was removed
under reduced pressure, and the product was purified
by recrystallization from propan-2-ol. Yield 0.45 g
(93%), mp 113–115°C, Rf 0.12 (diethyl ether), 0.40
(propan-2-ol). IR spectrum, ν, cm–1: 3320, 1780, 1735,
8. Petrova, T., Tarabara, I., Palchikov, V., Kasyan, L.,
Kosenkov, D., Okovytyi, S., Gorb., L. Shishkina, S.,
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kin, O.V., Kol’tsov, N.Yu., and Kas’yan, L.I., Russ. J.
Org. Chem., 2007, vol. 43, p. 660.
1
1420, 1380, 1270, 1170, 1040. H NMR spectrum, δ,
2
ppm: 1.66 d (1H, anti-8-H, J = 11.6 Hz), 1.88 d (1H,
10. Fristand, W.E. and Peterson, J.R., Tetrahedron, 1984,
syn-8-H), 2.03 s (3H, exo-AcO), 2.59 br.s (1H, 1-H),
vol. 40, p. 1469.
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REACTION OF N-SUBSTITUTED exo-2-HYDROXY-5-OXO-4-OXATRICYCLO...
829
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